Recursion said it will end development for four of its 11 pipeline programs—one of which the company will consider outlicensing to a partner instead—and pause a fifth program, in a pruning designed to further focus the artificial intelligence (AI)-based drug developer on cancer and rare disease treatments.
The company said it will end efforts to develop three clinical programs and one preclinical program:
The program halts will shrink Recursion’s pipeline to six active programs—four in cancer and two in rare diseases. The company also has a seventh pipeline program REC-4539, an LSD1 inhibitor designed to treat small-cell lung cancer, but says it is pausing the program pending emerging clinical data.
“Rare disease and oncology indications have been our consistent focus for a while, and this strategic prioritization is a disciplined way of continuing on high-impact opportunities across these therapeutic areas,” Recursion co-founder and CEO Chris Gibson, PhD, told GEN Edge.
The pipeline pruning comes six months after Recursion combined with AI pioneer Exscientia in a deal completed in November. The combined company trimmed its workforce down to roughly 800, compared with 900 pre-combination. A presentation to shareholders in October broke down the workforce as more than 500 at Recursion and more than 350 at Exscientia.
Asked whether Recursion will carry out further reductions in workforce this year, Gibson replied: “Given our cross-functional structure, the wind-down of certain programs will lead to project completions and team reassignments. We will continue to evaluate and adapt our resourcing to ensure quality delivery on prioritized programs.”
Back in February, Recursion presented positive data for REC-994 from the Phase II SYCAMORE trial (NCT05085561), showing 50% of patients achieving a reduction in mean lesion volume after 12 months of treatment and improved functional outcome at the 400 mg dose. The presentation took place at the International Stroke Conference (ISC) in Los Angeles, five months after Recursion announced in September 2024 that REC-994 met its primary endpoint of safety and tolerability in CCM patients with no treatment-related discontinuations or grade 3 adverse events.
Now, however, Recursion said long-term extension results from SYCAMORE showed no promising trends in MRI or functional outcome in patients crossing over from placebo to the 400 mg dose. Worse, the study’s 400 mg-to-400 mg arm did not sustain initial promising results and was indistinguishable from natural history. Data was not statistically significant at the 200 mg dose because SYCAMORE was not designed for statistical significance.
“While we saw some promising signals in the exploratory study, there were small [numbers of patients] in the heterogeneous population and the trend did not replicate in the placebo-400 [mg] arm for the long-term extension study,” Gibson explained. “Given our portfolio strategy and our data-driven approach, without a definitive signal, we did not think it prudent to go forward.”
REC-2282 had been under study in the Phase II/III POPLAR-NF2 trial (NCT05130866), which began in 2022 and read out Phase II data earlier this year. The study’s 40 mg cohort passed the futility threshold, but not the 60 mg and combined dose arms.
Why didn’t Recursion opt to refocus development of REC-2282 on the 40 mg dose, or look into a smaller dose?
“Despite meeting the futility criteria, we saw limited tumor shrinkage and clinical activity. Therefore, we are not seeking further development of the program,” Gibson said. “In short, the totality of the data supports discontinuing the study given other exciting programs in our pipeline that are more deserving of the resources.”
REC-3964 advanced to Phase II last fall, when the first patient was dosed in the Phase II ALDER trial (NCT06536465). REC-3964 is Recursion’s first new chemical entity to be developed through its RecursionOS Operating System, and had been designed to treat C. diff by selectively inhibiting the glucosyltransferase activity of toxin B produced by the bacterium in the gastrointestinal tract, offering a different mechanism of action from antibiotics.
However, REC-3964 was part of an increasingly crowded field of drugs and vaccines in development against C. diff, including candidates from Crestone Pharmaceuticals (positive Phase II results last September) and Pfizer, whose C. diff vaccine PF-06425090 failed the Phase III CLOVER trial (NCT03090191) last year. Also, existing treatments had resulted in low recurrence rates for C.diff, thus limiting the need for REC-3964
Recursion said it did not halt REC-3964 due to any clinical setbacks, but due to a strategic decision to focus on other areas deemed to have greater need for new treatments.
“This decision [to halt REC-3964 development] was entirely strategic based on the recent breakthroughs of other molecules in the C. diff space, reducing the unmet need in the space,” Gibson said. “The competitive breakthroughs are great news for patients!”
REC-4209 had been the subject of ongoing IND-enabling studies, with Recursion showing preclinical efficacy in a bleomycin lung fibrosis mouse model.
The company’s pipeline will now consist of:
On May 4, Recursion presented preliminary data at DDW 2025 from the ongoing Ib/II trial TUPELO trial (NCT05552755), showing REC-4881 (4 mg QD) leading to a preliminary median 43% reduction in polyp burden among six patients studied at the week 13 assessment. Five of six patients (83%) experienced reductions in polyp burden ranging from 31% to 82%, though the sixth showed a substantial increase from baseline.
Recursion will receive $7 million from Sanofi after advancing the fourth of 15 planned programs into the lead optimization phase in less than a year, as part of a collaboration that could generate more than $5.2 billion for the AI-based drug developer.
Recursion said it earned its latest milestone payout by identifying differentiated, oral small molecule leads against a target the company described as a high-interest immune cell target in immunology and inflammation (I&I) with best-in-class potential. Through profiling, the leads showed meaningful differentiation compared to current clinical I&I candidates, the company added.
The company carries out profiling through its Recursion OS, an AI drug discovery platform designed to industrialize drug discovery by continuously generating what, according to Recursion, is one of the world’s largest proprietary biological and chemical datasets.
Recursion applies machine-learning algorithms with the aim of distilling from its dataset trillions of searchable relationships across biology and chemistry, removed from human bias.
“Using the Recursion OS small molecule platform, within 10 months, we identified differentiated orally active small molecule leads with an order of magnitude improved target potency in the most relevant (and most challenging) cellular system,” Gibson said.
“The lead series is also much more selective against off-targets than known competition,” Gibson added. “These novel features place the program in an optimal position to meet its next milestone.”
Recursion co-founder and CEO Chris Gibson, PhD
The program achieved its lead optimization milestone in less than 10 months after the start of molecule design, Recursion added. Gibson contrasted that with the 18-to-24-month industry average of taking programs from lead optimization to a development candidate ready for investigational new drug (IND)-enabling studies.
“Under traditional industry timelines, the process from idea to lead can take years: Assays have to be built, bona fide hits have to be found—in silico and experimentally—and those hits have to undergo initial optimization, transformed into patentable chemical space, and tested in vivo for initial efficacy,” Gibson said.
“We believe we can dramatically shorten this time and cost to development candidate as we’ve demonstrated with numerous programs,” he added. “We’re measuring ourselves against industry averages and looking at where we can apply AI tools to bring greater speed and efficiency.”
A key example, according to Recursion, is its oncology candidate REC-1245, which is designed to treat biomarker-enriched solid tumors and lymphoma by targeting RBM39, a novel CDK12-adjacent target identified by Recursion OS.
Following FDA clearance of its IND application last fall, REC-1245 advanced to the start of a Phase I/II trial (NCT06678659) in just 18 months with only 200 compounds synthesized, compared to the industry standard of 42 months cited in a 2010 study, and thousands of compounds.
The Sanofi collaboration marries Sanofi’s global biopharma development expertise with a combined version of Recursion OS that applies Recursion’s AI-powered biological insights based on real-world patient data in tandem with Exscientia’s AI-driven chemical design.
“As part of this collaboration, Sanofi and Recursion discuss new targets and pathways collaboratively, ultimately arriving at the selected targets and target product profiles together. Sanofi and Recursion mutually agree when bringing projects forward,” Gibson explained.
Once Recursion and Sanofi identify a target, Recursion is responsible for leading the design, translational, and early preclinical studies to determine development candidates. Once Sanofi selects a development candidate, it will oversee IND-enabling studies and clinical development, manufacturing, and commercialization of that candidate at its own cost and expense.
The $7 million payout will bring the total to $30 million in early program milestone payments earned by Recursion in its collaboration with Sanofi.
The up to $5.2 billion-plus partnership took its present size when launched in 2022 with Exscientia, with Sanofi paying Exscientia $100 million in upfront cash. Now, Recursion is continuing where Exscientia left off in partnering with Sanofi to develop up to 15 novel small molecule candidates across oncology and immunology indications.
In October, Exscientia received a combined $15 million in milestone payments by advancing two Sanofi-partnered discovery programs (one in I&I, the other in oncology) into lead optimization, out of three Sanofi-partnered programs that had reached milestones totaling $23 million at the end of last year, Recursion stated in its Form 10-K annual report for 2024, filed February 28.
Earlier in 2024, Gibson added, Exscientia received a $4 million upfront payment after adding an existing program into the Sanofi collaboration that it had identified and initially advanced, “with compounds showing good potency and selectivity toward the target and differentiated molecular properties.”
Recursion said it remains eligible to receive additional payments of more than $300 million tied to achieving pre-commercial milestones, commercial milestone payments of over $300 million, as well as tiered royalties on product sales ranging from high-single-digits to mid-teens, subject to achieving specified research, development, regulatory, and commercial milestones.
In its collaboration with Sanofi, Recursion is responsible for taking projects through the development candidate stage. Sanofi is responsible for taking development candidates through IND studies and ultimately into the clinic.
Under an amendment to the companies’ collaboration and license agreement, Sanofi has agreed to use “commercially reasonable” efforts to obtain regulatory approval for at least one qualifying small molecule product in at least one agreed-upon major market. The companies have also agreed to use Recursion’s precision medicine platform for patient enrichment in Sanofi’s non-small molecule programs.
Sanofi is among biopharma giants that have shelled out more than a combined $450 million in upfront and milestone payments to Recursion and Exscientia through partnerships, with the potential to receive more than approximately $20 billion in additional milestone payments before royalties.
More than half of that total consists of the up-to-$12 billion partnership launched by Recursion in 2021 with Roche and its Genentech subsidiary. Other partners include big-name biopharma companies such as Bayer, Bristol Myers Squibb, Merck KGaA, and Sanofi.
Exscientia brought to the Sanofi collaboration a six-year relationship that began in 2016. A year later, Sanofi and Exscientia signed a potentially €250 million ($284 million) collaboration and license option to discover bispecific small-molecule drugs against metabolic diseases. And in 2019, Sanofi in-licensed Exscientia’s bispecific small molecule candidate designed to target two distinct targets in inflammation and immunology.
The value of the Recursion-Exscientia deal has not been formally disclosed by the companies, though Reuters and CNBC reported the transaction as being $688 million when it was first announced in August 2024.
The post Recursion Halts Four Pipeline Programs, Sharpening Cancer, Rare Disease Focus appeared first on GEN - Genetic Engineering and Biotechnology News.
The company said it will end efforts to develop three clinical programs and one preclinical program:
- REC-994—a Phase II oral, non-antibiotic small molecule superoxide scavenger being developed to treat symptomatic cerebral cavernous malformation (CCM).
- REC-2282—a Phase II oral, CNS penetrant small molecule pan-histone deacetylase (HDAC) inhibitor designed to treat progressive neurofibromatosis type 2 (NF2)-mutated meningiomas
- REC-3964—a Phase II oral, potential first-in-class, non-antibiotic small molecule designed to selectively inhibit Clostridioides difficile (C.diff) toxin B (TcdB) in the gastrointestinal tract
- REC-4209—a preclinical oral, reversible, potential first-in-class candidate for idiopathic pulmonary fibrosis (IPF), whose target was undisclosed except for its name, Epsilon.
The program halts will shrink Recursion’s pipeline to six active programs—four in cancer and two in rare diseases. The company also has a seventh pipeline program REC-4539, an LSD1 inhibitor designed to treat small-cell lung cancer, but says it is pausing the program pending emerging clinical data.
“Rare disease and oncology indications have been our consistent focus for a while, and this strategic prioritization is a disciplined way of continuing on high-impact opportunities across these therapeutic areas,” Recursion co-founder and CEO Chris Gibson, PhD, told GEN Edge.
Combined with Exscientia
The pipeline pruning comes six months after Recursion combined with AI pioneer Exscientia in a deal completed in November. The combined company trimmed its workforce down to roughly 800, compared with 900 pre-combination. A presentation to shareholders in October broke down the workforce as more than 500 at Recursion and more than 350 at Exscientia.
Asked whether Recursion will carry out further reductions in workforce this year, Gibson replied: “Given our cross-functional structure, the wind-down of certain programs will lead to project completions and team reassignments. We will continue to evaluate and adapt our resourcing to ensure quality delivery on prioritized programs.”
Back in February, Recursion presented positive data for REC-994 from the Phase II SYCAMORE trial (NCT05085561), showing 50% of patients achieving a reduction in mean lesion volume after 12 months of treatment and improved functional outcome at the 400 mg dose. The presentation took place at the International Stroke Conference (ISC) in Los Angeles, five months after Recursion announced in September 2024 that REC-994 met its primary endpoint of safety and tolerability in CCM patients with no treatment-related discontinuations or grade 3 adverse events.
Now, however, Recursion said long-term extension results from SYCAMORE showed no promising trends in MRI or functional outcome in patients crossing over from placebo to the 400 mg dose. Worse, the study’s 400 mg-to-400 mg arm did not sustain initial promising results and was indistinguishable from natural history. Data was not statistically significant at the 200 mg dose because SYCAMORE was not designed for statistical significance.
“While we saw some promising signals in the exploratory study, there were small [numbers of patients] in the heterogeneous population and the trend did not replicate in the placebo-400 [mg] arm for the long-term extension study,” Gibson explained. “Given our portfolio strategy and our data-driven approach, without a definitive signal, we did not think it prudent to go forward.”
REC-2282 had been under study in the Phase II/III POPLAR-NF2 trial (NCT05130866), which began in 2022 and read out Phase II data earlier this year. The study’s 40 mg cohort passed the futility threshold, but not the 60 mg and combined dose arms.
Limited tumor shrinkage
Why didn’t Recursion opt to refocus development of REC-2282 on the 40 mg dose, or look into a smaller dose?
“Despite meeting the futility criteria, we saw limited tumor shrinkage and clinical activity. Therefore, we are not seeking further development of the program,” Gibson said. “In short, the totality of the data supports discontinuing the study given other exciting programs in our pipeline that are more deserving of the resources.”
REC-3964 advanced to Phase II last fall, when the first patient was dosed in the Phase II ALDER trial (NCT06536465). REC-3964 is Recursion’s first new chemical entity to be developed through its RecursionOS Operating System, and had been designed to treat C. diff by selectively inhibiting the glucosyltransferase activity of toxin B produced by the bacterium in the gastrointestinal tract, offering a different mechanism of action from antibiotics.
However, REC-3964 was part of an increasingly crowded field of drugs and vaccines in development against C. diff, including candidates from Crestone Pharmaceuticals (positive Phase II results last September) and Pfizer, whose C. diff vaccine PF-06425090 failed the Phase III CLOVER trial (NCT03090191) last year. Also, existing treatments had resulted in low recurrence rates for C.diff, thus limiting the need for REC-3964
Recursion said it did not halt REC-3964 due to any clinical setbacks, but due to a strategic decision to focus on other areas deemed to have greater need for new treatments.
“Entirely strategic”
“This decision [to halt REC-3964 development] was entirely strategic based on the recent breakthroughs of other molecules in the C. diff space, reducing the unmet need in the space,” Gibson said. “The competitive breakthroughs are great news for patients!”
REC-4209 had been the subject of ongoing IND-enabling studies, with Recursion showing preclinical efficacy in a bleomycin lung fibrosis mouse model.
The company’s pipeline will now consist of:
- REC-617, a Phase I/II CDK7 inhibitor being developed to treat multiple advanced solid tumor indications
- REC-1245, a Phase I treatment for biomarker-enhanced solid tumors and lymphoma that is a selective degrader of RNA binding motif protein 39 (RBM39), a novel CDK12-adjacent target identified by the company’s Recursion Operating System (OS) platform
- REC-3565, a Phase I small molecule MALT1 inhibitor being developed for multiple blood cancer indications
- REC-7735, a preclinical program targeting PI3Ka H1047R mutant breast cancer, for which a development candidate is expected to be nominated in the second half of this year
- REV102, an oral, small molecule ENPP1 inhibitor being developed for the treatment of hypophosphatasia (HPP)
- REC-4881, an oral non-ATP-competitive, allosteric small molecule inhibitor of MEK1 and MEK2 is being developed to reduce polyp burden and progression to adenocarcinoma in people living with Familial Adenomatous Polyposis (FAP)
On May 4, Recursion presented preliminary data at DDW 2025 from the ongoing Ib/II trial TUPELO trial (NCT05552755), showing REC-4881 (4 mg QD) leading to a preliminary median 43% reduction in polyp burden among six patients studied at the week 13 assessment. Five of six patients (83%) experienced reductions in polyp burden ranging from 31% to 82%, though the sixth showed a substantial increase from baseline.
Recursion advances fourth Sanofi-partnered program
Recursion will receive $7 million from Sanofi after advancing the fourth of 15 planned programs into the lead optimization phase in less than a year, as part of a collaboration that could generate more than $5.2 billion for the AI-based drug developer.
Recursion said it earned its latest milestone payout by identifying differentiated, oral small molecule leads against a target the company described as a high-interest immune cell target in immunology and inflammation (I&I) with best-in-class potential. Through profiling, the leads showed meaningful differentiation compared to current clinical I&I candidates, the company added.
The company carries out profiling through its Recursion OS, an AI drug discovery platform designed to industrialize drug discovery by continuously generating what, according to Recursion, is one of the world’s largest proprietary biological and chemical datasets.
Recursion applies machine-learning algorithms with the aim of distilling from its dataset trillions of searchable relationships across biology and chemistry, removed from human bias.
“Using the Recursion OS small molecule platform, within 10 months, we identified differentiated orally active small molecule leads with an order of magnitude improved target potency in the most relevant (and most challenging) cellular system,” Gibson said.
“Optimal position”
“The lead series is also much more selective against off-targets than known competition,” Gibson added. “These novel features place the program in an optimal position to meet its next milestone.”
Recursion co-founder and CEO Chris Gibson, PhD
The program achieved its lead optimization milestone in less than 10 months after the start of molecule design, Recursion added. Gibson contrasted that with the 18-to-24-month industry average of taking programs from lead optimization to a development candidate ready for investigational new drug (IND)-enabling studies.
“Under traditional industry timelines, the process from idea to lead can take years: Assays have to be built, bona fide hits have to be found—in silico and experimentally—and those hits have to undergo initial optimization, transformed into patentable chemical space, and tested in vivo for initial efficacy,” Gibson said.
“We believe we can dramatically shorten this time and cost to development candidate as we’ve demonstrated with numerous programs,” he added. “We’re measuring ourselves against industry averages and looking at where we can apply AI tools to bring greater speed and efficiency.”
A key example, according to Recursion, is its oncology candidate REC-1245, which is designed to treat biomarker-enriched solid tumors and lymphoma by targeting RBM39, a novel CDK12-adjacent target identified by Recursion OS.
Following FDA clearance of its IND application last fall, REC-1245 advanced to the start of a Phase I/II trial (NCT06678659) in just 18 months with only 200 compounds synthesized, compared to the industry standard of 42 months cited in a 2010 study, and thousands of compounds.
The Sanofi collaboration marries Sanofi’s global biopharma development expertise with a combined version of Recursion OS that applies Recursion’s AI-powered biological insights based on real-world patient data in tandem with Exscientia’s AI-driven chemical design.
“As part of this collaboration, Sanofi and Recursion discuss new targets and pathways collaboratively, ultimately arriving at the selected targets and target product profiles together. Sanofi and Recursion mutually agree when bringing projects forward,” Gibson explained.
Once Recursion and Sanofi identify a target, Recursion is responsible for leading the design, translational, and early preclinical studies to determine development candidates. Once Sanofi selects a development candidate, it will oversee IND-enabling studies and clinical development, manufacturing, and commercialization of that candidate at its own cost and expense.
$30M in milestone payments
The $7 million payout will bring the total to $30 million in early program milestone payments earned by Recursion in its collaboration with Sanofi.
The up to $5.2 billion-plus partnership took its present size when launched in 2022 with Exscientia, with Sanofi paying Exscientia $100 million in upfront cash. Now, Recursion is continuing where Exscientia left off in partnering with Sanofi to develop up to 15 novel small molecule candidates across oncology and immunology indications.
In October, Exscientia received a combined $15 million in milestone payments by advancing two Sanofi-partnered discovery programs (one in I&I, the other in oncology) into lead optimization, out of three Sanofi-partnered programs that had reached milestones totaling $23 million at the end of last year, Recursion stated in its Form 10-K annual report for 2024, filed February 28.
Earlier in 2024, Gibson added, Exscientia received a $4 million upfront payment after adding an existing program into the Sanofi collaboration that it had identified and initially advanced, “with compounds showing good potency and selectivity toward the target and differentiated molecular properties.”
Recursion said it remains eligible to receive additional payments of more than $300 million tied to achieving pre-commercial milestones, commercial milestone payments of over $300 million, as well as tiered royalties on product sales ranging from high-single-digits to mid-teens, subject to achieving specified research, development, regulatory, and commercial milestones.
In its collaboration with Sanofi, Recursion is responsible for taking projects through the development candidate stage. Sanofi is responsible for taking development candidates through IND studies and ultimately into the clinic.
“Commercially reasonable”
Under an amendment to the companies’ collaboration and license agreement, Sanofi has agreed to use “commercially reasonable” efforts to obtain regulatory approval for at least one qualifying small molecule product in at least one agreed-upon major market. The companies have also agreed to use Recursion’s precision medicine platform for patient enrichment in Sanofi’s non-small molecule programs.
Sanofi is among biopharma giants that have shelled out more than a combined $450 million in upfront and milestone payments to Recursion and Exscientia through partnerships, with the potential to receive more than approximately $20 billion in additional milestone payments before royalties.
More than half of that total consists of the up-to-$12 billion partnership launched by Recursion in 2021 with Roche and its Genentech subsidiary. Other partners include big-name biopharma companies such as Bayer, Bristol Myers Squibb, Merck KGaA, and Sanofi.
Exscientia brought to the Sanofi collaboration a six-year relationship that began in 2016. A year later, Sanofi and Exscientia signed a potentially €250 million ($284 million) collaboration and license option to discover bispecific small-molecule drugs against metabolic diseases. And in 2019, Sanofi in-licensed Exscientia’s bispecific small molecule candidate designed to target two distinct targets in inflammation and immunology.
The value of the Recursion-Exscientia deal has not been formally disclosed by the companies, though Reuters and CNBC reported the transaction as being $688 million when it was first announced in August 2024.
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